Aflatoxin and other mycotoxins commonly contaminate grains and other foods and may be carcinogenic or otherwise hazardous to health. It is known that both adult animals and their young are suceptible to these agents. Since mycotoxins are rarely found singularly in nature, the current proposal emphasizes studies of multiple exposures to one or two agents by feeding to pregnant rats and administration parenterally to neonatal pups in maximally tolerated doses. The investigations will describe the carcinogenicity of each agent and the interactions of paired agents during pre- and postnatal development. To quantitate and evaluate mechanisms, cross-over experiments will determine whether prenatal or postnatal exposures to carcinogens are more likely to induce tumor development in later life. Concentrations of carcinogens and their metabolites will be measured in fetal tissues and intrauterine fluids and in mammary secretions. In experiments to determine maximally tolerated doses, the toxicology of each agent will be described in rats at various stages of development; minimally effective doses will be established in order to relate tumorigenesis and other toxic manifestations to population exposures. Toxicological investigations will be undertaken to determine metabolic alterations such as changes in enzyme activity and changes in cellular respiration produced by mixtures of these compounds. With this, knowledge of the causal chain of events leading to tumor formation or illness can be examined. The metabolic reactions which modify the toxicity of these environmental toxins and their effect on the mechanism of toxicity can then be considered. It is only by knowing the mechanism of toxicity and/or carcinogenicity that an intelligent approach to eliminating or, at least, decreasing toxic hazards can be undertaken. BIBLIOGRAPHIC REFERENCES: Farb, R.M., J.L. Mego and A.W. Hayes. 1976. Effect of mycotoxins in uptake and degradation of 125I-albumin in mouse liver and kidney lysosomes. J. Toxicol. Environ. Health. Hayes, A.W. and R.D. Hood. 1976. Effect of prenatal exposure to mycotoxins. Proceed. Europ. Soc. Toxicol.